Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of 14Caficamten following single oral dose administration to rats

The pharmacokinetics, metabolism, excretion, mass balance, and tissue distribution of [14C]aficamten were evaluated following oral administration of an 8 mg/kg dose in Sprague Dawley rats and in a quantitative whole-body autoradiography study in Long Evans rats.[14C]Aficamten accounted for ∼80% and...

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Bibliographic Details
Published in:Xenobiotica 2024-09, Vol.54 (9), p.670
Main Authors: Grillo, Mark P, Sukhun, Rajaa, Bashir, Mohammad, Ashcraft, Luke, Morgan, Bradley P
Format: Article
Language:English
Online Access:Get full text
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Summary:The pharmacokinetics, metabolism, excretion, mass balance, and tissue distribution of [14C]aficamten were evaluated following oral administration of an 8 mg/kg dose in Sprague Dawley rats and in a quantitative whole-body autoradiography study in Long Evans rats.[14C]Aficamten accounted for ∼80% and a hydroxylated metabolite (M1) accounted for ∼12% of total radioactivity in plasma over 48-h (AUC0-48). Plasma tmax was 4-h and the t1/2 of total plasma radioactivity was 5.8-h.Tissues showing highest Cmax exposures were myocardium and semitendinosus muscle.Most [14C]aficamten-derived radioactivity was excreted within 48-h post-administration. Mean cumulative recovery in urine and faeces over 168-h was 8.3% and 90.7%, respectively.In urine and bile, unchanged aficamten was detected at
ISSN:1366-5928
1366-5928
DOI:10.1080/00498254.2024.2381111